Background and Aims

Primary biliary cholangitis (PBC) is a slowly progressing cholestatic, autoimmune liver disease, characterized by the presence of anti-mitochondrial (AMA) and antinuclear antibodies (ANA) in the patients sera. The aim of the study was to determine the autoantibodies reactive against novel potential autoantigen in PBC - kelch-like 12 (KLHL12) protein in a well characterized cohort of PBC patients and compare them with other specific autoantibodies and biochemical parameters.

Methods

Study population - 92 PBC patients, 30 pathological controls – 20 primary sclerosing cholangitis (PSC) and 10 autoimmune hepatitis (AIH) patients, 30 healthy blood donors.

AMA, anti-Sp100 and anti-gp210 were detected by commercially available kits (IMTEC-Human, Euroimmun; Germany and Inova Diagnostics; USA). The presence of anti- KLHL12 antibody was determined by an” in-house” ELISA technique using a full-length recombinant human KLHL12 protein.

Results

Anti-KLHL12 antibodies were detected in 35% of the total cohort of PBC patients, including AMA-negative PBC. They were found more frequently in PBC compared with non-PBC disease controls (P < 0.001). Specificity and positive predictive values of this test for PBC were 98% and 96%, respectively. We found anti-KLHL12 antibodies together with anti-Sp100 and/or anti-gp210 in 59 (64%) cases. Presence of anti-KLHL12 was associated with higher concentration of bilirubin and correlate with fibrosis (P<0.05).

Conclusions

Antibodies against KLHL12 protein are highly specific for PBC. The combination of anti-KLHL12 with other markers can increase the diagnostic sensitivity on PBC. Coexistence of different antibodies suggests an autoimmune reaction against multiple nuclear components in some of PBC patients.